The framework – outlined in a suite of four guidance documents – builds upon the FDA’s existing risk-based regulatory approach to more clearly describe what products are regulated as drugs, devices, and/or biological products. Further, two of the guidance documents propose an efficient, science-based process for helping to ensure the safety and effectiveness of these therapies, while supporting development in this area. The suite of guidance documents also defines a risk-based framework for how the FDA intends to focus its enforcement actions against those products that raise potential significant safety concerns. This modern framework is intended to balance the agency’s commitment to safety with mechanisms to drive further advances in regenerative medicine so innovators can bring new, effective therapies to patients as quickly and safely as possible. The policy also delivers on important provisions of the 21st Century Cures Act.

“We’re at the beginning of a paradigm change in medicine with the promise of being able to facilitate regeneration of parts of the human body, where cells and tissues can be engineered to grow healthy, functional organs to replace diseased ones; new genes can be introduced into the body to combat disease; and adult stem cells can generate replacements for cells that are lost to injury or disease. This is no longer the stuff of science fiction. This is the practical promise of modern applications of regenerative medicine,” said FDA Commissioner Scott Gottlieb, M.D. “But this field is dynamic and complex. As such, it has presented unique challenges to researchers, health care providers, and the FDA as we seek to provide a clear pathway for those developing new therapies in this promising field, while making sure that the FDA meets its obligation to ensure the safety and efficacy of the medical products that patients rely upon. Alongside all the promise, we’ve also seen products marketed that are dangerous and have harmed people. With the policy framework the FDA is announcing today, we’re adopting a risk-based and science-based approach that builds upon existing regulations to support innovative product development while clarifying the FDA’s authorities and enforcement priorities. This will protect patients from products that pose potential significant risks, while accelerating access to safe and effective new therapies.”

The framework includes two final guidance documents and two draft guidance documents.

New Final Guidance Documents
The two final guidance documents clarify the FDA’s interpretation of the risk-based criteria manufacturers use to determine whether a product is subject to the FDA’s premarket review.
The first guidance provides greater clarity around when cell and tissue-based products would be excepted from the established regulations if they are removed from and implanted into the same individual within the same surgical procedure and remain in their original form. The second final guidance helps stakeholders better understand how existing regulatory criteria apply to their products by clarifying how the agency interprets the existing regulatory definitions “minimal manipulation” and “homologous use.” As this field advances, the FDA has noted that there are a growing number of regenerative medicine products subject to FDA premarket authorization. These guidance documents will help explain how the FDA will provide a risk-based framework for its oversight. The policy framework defines how we intend to take action against unsafe products while facilitating continued innovation of promising technologies…New Draft Guidance Documents
The two draft guidances provide important information to help spur development and access to innovative regenerative therapies. The first draft guidance, which builds off the regenerative medicine provisions in the 21st Century Cures Act, addresses how the FDA intends to simplify and streamline its application of the regulatory requirements for devices used in the recovery, isolation, and delivery of regenerative medicine advanced therapies (RMATs), including combination products. The guidance specifies that devices intended for use with a specific RMAT may, together with the RMAT, be considered to comprise a combination product.

Given this area’s rapid growth, dynamism and complexity, this field has also presented unique challenges to researchers, health care providers and the FDA. We need to provide a clear, efficient pathway for product developers, while making sure that we meet our obligation to help ensure the safety and efficacy of these medical products so that patients can benefit from these novel therapies.

To achieve these goals, today we’re taking steps to advance an innovative framework for how we intend to apply the existing laws and regulations that govern these products. Our aim is to make sure we’re being nimble and creative when it comes to fostering innovation, while taking steps to protect the safety of patients.

The FDA originally established a regulatory framework for these products that went into effect in 2005. But in the last decade, we’ve seen improbable advances that hold out great hope for patients. I believe that with the ability to facilitate the regeneration of parts of the human body, we’re bearing witness to the beginning of a paradigm shift in the practice of medicine.

These concepts are no longer the stuff of science fiction, but rather real-life science where cells and tissues can be engineered to grow healthy, functional organs to replace diseased ones; where new genes can be introduced into the body to combat disease; and where adult stem cells can generate replacements for cells that are lost to injury or illness. The promise of this technology is why the FDA is so committed to encouraging and supporting innovation in this field.

But the rapid growth and promise of this field has increasingly sowed the ground for the entry of some unscrupulous actors, who have opportunistically seized on the clinical potential of regenerative medicine to make deceptive claims to patients about unproven and, in some cases, dangerous products. By exploiting the lack of consumer understanding of this area, as well as the fear and uncertainties posed by the diseases these bad actors claim to treat, they’re jeopardizing the legitimacy and advancement of the entire field. This underscores the importance of having a clear regulatory framework for developers, and ensuring that those who skirt these regulations are held accountable.

To realize the full potential of regenerative medicine, we need to support the innovation pursued by responsible product developers – who represent the vast majority of the field – to help ensure that they clearly understand where the regulatory lines are drawn. We must advance a modern, efficient and least burdensome framework that recognizes the breakneck speed of advancement in the products we’re being asked to evaluate, while ensuring patient safety. That is the goal of the policy we’re announcing today.

To achieve this balance, embedded in our comprehensive framework are many proposed novel and modern approaches to regulation, where we intend to adapt our regulatory model to meet the revolutionary nature of the products we’re being asked to evaluate.

One example is how we’re considering innovative trial designs whereby individual academic investigators would follow the same manufacturing protocols and share combined clinical trial data in support of approval from the FDA. This is an innovative way of making sure that small investigators who are working with cells that are being manufactured in ways that render them subject to our current laws and regulations — because the cells are, for example, more than “minimally manipulated” — can nonetheless seek the FDA’s approval through a less burdensome process.

There are other similarly proposed novel approaches embedded in our broad policy framework. Our goal is to achieve a risk-based and science-based approach to support innovative product development, while clarifying the FDA’s authorities and enforcement priorities and making sure we are protecting patients.

We understand that there will be questions and it will take time for product developers to determine whether their products require FDA approval. Our policy will allow product manufacturers that time to engage with the FDA to determine if they need to submit a marketing authorization application and, if so, seek guidance on how to submit their application to the FDA for approval.

To be clear, we remain committed to ensuring that patients have access to safe and effective regenerative medicine products as efficiently as possible. We are also committed to making sure we take action against products being unlawfully marketed that pose a potential significant risk to their safety. The framework we’re announcing today gives us the solid platform we need to continue to take enforcement action against a small number of clearly unscrupulous actors.
With this balanced approach, we’re well positioned to support and help advance breakthrough science, like regenerative medicine, and promote responsible and flexible regulation that leverages science to advance public health…:::::: ::::::